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OVERVIEW

The breakdown (catabolism) and synthesis (anabolism) of carbohydrate molecules represent the primary means for the human body to store and utilize energy and to provide building blocks for molecules such as nucleotides (Figure 6-1). The enzyme reactions that form the metabolic pathways for monosaccharide carbohydrates (Chapter 2) include glycolysis, the citric acid cycle, and oxidative phosphorylation as the main means to produce the energy molecule adenosine triphosphate (ATP). Gluconeogenesis and the pentose phosphate pathway represent the two main anabolic pathways to produce new carbohydrate molecules. Glycogen has its own metabolic pathway for lengthening, shortening, and/or adding branch points in the carbohydrate chain(s). Not surprisingly, all of these processes are highly regulated at multiple points to allow the human body to efficiently utilize these important biomolecules. Finally, many modified carbohydrates are part of a variety of surface and cytosolic signaling molecules, including glycoproteins and glycosaminoglycans (GAGs) (Chapter 2). These important carbohydrate molecules and the control points in carbohydrate and glycoprotein metabolism, therefore, present clinicians with opportunities to modify these many reactions to improve health or to fight disease.

Figure 6-1.

Overview of Carbohydrate Metabolism. Glucose from the diet can be metabolized via glycolysis or glycogenesis. Resulting metabolic products can return to glucose via gluconeogenesis or glycogenolysis, respectively, or proceed further along carbohydrate metabolism to the citric acid cycle. Alternatively, glucose products can be shunted off to fat or amino acid metabolism as indicated. Details are discussed in the text and other chapters. [Adapted with permission from Murray RA, et al.: Harper’s Illustrated Biochemistry, 28th edition, McGraw-Hill, 2009.]

GLYCOLYSIS

Glycolysis is the metabolic pathway that breaks down (catabolism) hexose (six-carbon) monosaccharides such as glucose, fructose, and galactose into two molecules of pyruvate, two molecules of ATP, two molecules of NADH, two water (H2O) molecules, and two hydrogen ions (H+) (Figure 6-2). Glycolysis involves 10 enzyme-mediated steps and is best envisioned in two phases—phosphorylation and energy production—all of which occur in the cytoplasm. The phosphorylation phase (sometimes referred to as the preparatory phase) starts with the six-carbon carbohydrate glucose and involves two phosphorylations from ATP and the cleavage into two molecules of the triose (three-carbon sugar) glyceraldehyde-3-phosphate. The energy production phase involves the next five steps during which the two molecules of glyceraldehyde-3-phosphate are converted to two pyruvate molecules with the production of two NADH molecules and four ATP molecules. Glucose-6-phosphate, the first intermediate of glycolysis, cannot exit the cell-like glucose, so it also traps the glucose molecule in the cell for energy production via glycolysis or glycogen synthesis (see below). NADH represents an alternative energy storage form than ATP, which may be utilized by the oxidative phosphorylation pathway.

Figure 6-2.

Glycolysis. The pathway of glycolysis includes 10 enzyme steps, which ...

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